We reasoned that persistent exposure to a limited set of airborne antigens could drive the preferential expansion of single T-cell clones in the lower respiratory tract of normal individuals. To explore this issue, the normal human alpha/beta T-cell receptor repertoire was studied in lung lymphocytes obtained by bronchoalveolar lavage (BAL) from the humen of the lower respiratory tract. BAL T-cells obtained from five healthy volunteers were first analysed using polymerase chain reaction to amplify all known V alpha and V beta genes of the T-cell receptor. T-cells from peripheral blood were used as an internal control. Heteroduplex analysis of the amplified products was then performed, to assess the clonal composition of the repertoire of lung- versus blood-derived T-lymphocytes within each amplified variable gene family. In all subjects, the T-cell repertoire in the lung was largely as heterogeneous as peripheral blood in terms of clonal composition. This indicated lack of preferential expansion of single T-cell clones. A few T-cell clones were simultaneously expanded in blood and lung in all individuals within a limited number of V beta (mean 2.4; range 2-4) and V alpha (mean 1.6; range 1-3) genes. We also found that lung T-lymphocytes expressed all of the V gene families of the T-cell receptor that were expressed by peripheral blood T-cells. Our results indicate that T-cell clones in the lower respiratory tract of normal individuals are distributed according to a largely polyclonal pattern, which corresponds to that found in peripheral blood.
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http://dx.doi.org/10.1183/09031936.96.09020319 | DOI Listing |
Sci Data
January 2025
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
The distinctive characteristics of an individual's T cell receptor repertoire are crucial in recognizing and responding to a diverse array of antigens, contributing to immune specificity and adaptability. The repertoire, famously vast due to a series of cellular mechanisms, can be quantified using repertoire sequencing. In this study, we sampled the repertoire of 85 women: ovarian cancer patients (OC) and healthy donors (HD), generating a dataset of T cell clones and their abundance.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Herlev Hospital, Herlev, Denmark
Background: Arginase-1 (Arg1) expressing tumor-associated macrophages (TAMs) may create an immune-suppressive tumor microenvironment (TME), which is a significant challenge for cancer immunotherapy. We previously reported the existence of Arg1-specific memory T cells among peripheral blood mononuclear cells (PBMCs) and described that Arg-1-based immune modulatory vaccines (IMVs) control tumor growth and alter the M1/M2 macrophage ratio in murine models of cancer. In the present study, we investigated how Arg1-specific T cells can directly target TAMs and influence their polarization.
View Article and Find Full Text PDFSci Transl Med
January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Nanjing University, School of Chemistry and Chemical Engineering, CHINA.
T cells play a pivotal role in the development of autoimmune diseases. To mitigate autoimmune inflammation without inducing global immunosuppression, it is crucial to selectively eliminate autoreactive T cell clones while preserving the normal T cell repertoire. In this study, we applied cellular proximity chemistry to develop a T-cell depletion method with clonal precision.
View Article and Find Full Text PDFBackground: Ulcerative Colitis (UC) is characterized by chronic, relapsing and remitting inflammation in the colon and rectum. Pathogenic T cell activity is thought to play a major role in this process. T cell effector function is determined by the T cell receptor (TCR) and the antigen it recognizes.
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